ISSN 2249-1848
Mathi, et al. Int J Pharm 2015; 5(1): 265-273
International Journal of Pharmacy
Journal Homepage: http://www.pharmascholars.com
Review Article
CODEN: IJPNL6
MEDICINAL USES AND BIOLOGICAL ACTIVITIES OF SOPHORA INTERRUPTA
BEDD-A REVIEW
Pardhasaradhi Mathi 1, Venkata Raman Bokka 2 and Mahendran Botlagunta 1*
1
Biomedical research Laboratory, Department of Biotechnology, K L E F University, Green
fields, Vaddeswaram, Guntur 522502, AndhraPradesh, India
2
Department of Basic Sciences-Chemistry, Madanapalle Institute of Technology and Science
(MITS), Madanapalle, Chittoor 517325, AndhraPradesh, India
*Corresponding author e-mail: bmnchowdary@gmail.com
ABSTRACT
Sophora interrupta Bedd, was a common woody perennial herb native to India. Reports suggest that the plant
possesses numerous health promoting benefits such as anticancer, antiinflammatory, antimicrobial and antioxidant
activities. The plant exhibited several potential in vitro anticancer effects on MCF-7, PC-3, HeLa and HePG-2 cell
lines. In vivo assay’s suppressed in mouse models Dalton’s lymphoma ascites, along with acute toxicity studies,
central nervous system and hepatoprotective studies. The major phytoconstituents isolated from this plant are
prenylated flavonoids, chalcones, biochanin-A and Kaempferol. This review aims to concern about taxonomy,
cultivation, biological activities of the isolated compounds and to evaluate the current status of S. interrupta to give
a comprehensive view of its future development and further improvement of its suitability in curing a wide range of
ailments.
Keywords: Sophora interrupta, fabaceae, cancer, free radicals, cell lines.
INTRODUCTION
Approximately, more than 3000 plant species are
officially documented for its medicinal potential in
India[1]. Our traditional systems (3700 B.C) of
medicines, viz., Ayurveda, Yunani, Siddha and
Homeopathy etc. use herbs for treatment of wide
range of ailments. It was estimated that 40% of the
world populations depending directly on plant based
medicine for their health care[2]. According to the
WHO more than one million people rely on herbal
medicines to some extent and also listed 21,000
plants for medicinal uses around the world [3]. India
has a rich medicinal plant flora of around 150 species
and were commercially used for extracting medicines
or drug formulation [4]. Sophora interrupta belongs
to Fabaceae family was a very important shrub in the
Ayurveda and was highly studied by researchers in
India.
Taxonomy: The taxonomic status of S. interrupta
was well documented in table 1, Vernacular names:
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Adivibilla (Telugu), Pili Girgoli (Hawaiian).
Synonyms: Edwardsia maderaspatana Wight.
Origin and geographical source: Sophora genus
consists of approximately 36 species, distributed
throughout the globe (referring to table 2 with S.No)
which is clearly represented in the pictographic map
(Figure 1). Tirumala hills are part of Seshachalam
hills comprising of seven hills covered with dense
forests situated very close to each other with plenty
of Ayurvedic resources along with S. interrupta. The
total area of Tirumala hills was about 4,755.99 sq.
km. According to a study, it has been estimated that
over 1,700 species belonging to 178 families of
vascular
plants
exist
in
the
region
[http://www.thehindu.com/todays-paper/tp-inschool/rich-biodiversity-found-in-seshachalamforests/article3989461.ece]. And this plant was
endemically at higher altitudes such as at
Kumaradhara theertham, Sesha theertham, Kapila
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theertham and Talakona at sacred Tirumala hills [5,
6].
along with physicochemical parameters and
fluorescence analysis of root powder which helps to
establish diagnostic characters and quality parameters
for the identification of the powdered form of root.
TLC and HPTLC profile of Benzene extract was
performed for flavonoids. Powder of root material
showed the presence of xylem vessels with annular
and scalariform thickenings, cork cells, starch grains
and calcium oxalate crystals [7].
Morphological characteristics: S. interrupta grow to
a height of two and half meters covered with golden
yellow bell shaped flowers, comprising of auxiliaries
and terminal racemes. Pods are four winged
constricted between seeds. Seeds are 3-6, obovoid or
globbose and strophiole. The roots are woody,
tuberous, and perennial, about 4 to 8 cm in diameter,
light brownish yellow in color with characteristic
odor and highly bitter taste [7].
Propagation and planting: Species in this genus are
spread throughout the tropical and temperate regions
of the world. S. interrupta reported to flower at the
time of the winter season [8]. Plantations which are
planted apart from Tirumala are not propagating due
to the absence of native soil and natural conditions
i.e; endemic in nature (Unpublished observation).
Phytochemicals: Root and leaf extracts of this plant
contains several phytochemicals such as, alkaloids,
tannins, phenols, flavonoids, steroids, cardiac
glycosides and saponins which were estimated using
standard protocols. [7, 9].
PHARMACOLOGICAL ACTIVITIES
The generic name Sophora was derived from an
Arabic word “Sophera” means a pea-flowered tree
form. The leaf methanol extract of this plant
suppressed Dalton’s Ascitic Lymphoma in mouse
models. Only few compounds from this plant were
explored and if such medicinal plant correctly
engaged in research will generate novel insights for
treating various cancers. The current review aims to
give the best of our knowledge on (i) the genetic
diversity of the plant and Pharmacognostical studies.
(ii) Biological role in disease targeting (iii) Isolated
active components and its biological roles, which can
show a bright research path for future generations.
Sophora interrupta genetically diverse plant and
Pharmacognostical studies: The plant Sophora
genus was well explored all over the world almost
120 species. In which 57 species are still unexplored.
Sophora species are well distributed from eastern
part (Japan) to the western (Caribbean islands) part of
the world. Most the species, i.e.; 36 from this genus
are well explored with its geographical locations and
its latitude and longitude of origins (table 2). Still,
there is a need to explore and justify the putative
compounds present in Sophora interrupta plant.
Pharmacognostical studies explored the qualitative
and quantitative microscopic evaluation of the root
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Biological role in disease targeting: Sophora
interrupta was well reported to be in suppressing
cancer cell growth in cell lines as well as in albino
mouse models. All parts of the plant with different
solvent extracts have been reported to have many
biological activities which enables in potential
applications such as in treating Cancer (Dalton’s
lymphoma Ascites) by leaf and whole plant methanol
extract, cytotoxicity studies (HeLa and HepG2) cell
lines by whole plant methanol extract, MCF-7 cancer
cell lines, induction of apoptosis, and DNA
fragmentation by leaf aqueous extract. Acute oral
toxicity studies (Albino mice), ulcer (Wistar rats) by
defatted methanol extract, central nervous system
(CNS) on Swiss albino mice by the leaf methanol
extract, the Anthelmintic activity of methanol leaf
extracts on Pheritima posthuma. Hepatoprotective
activity in Male Wistar rats by leaf methanol extract.
However, reports on the biological activity on
different diseases are clearly included below
Anticancer property: Dalton’s lymphoma ascites
(DLA) is a tumor which was developed in the thymus
gland of a DBA/2 mouse at the National Cancer
Institute, Bethesda, US in 1947. Later on, an ascites
form was evolved by repeated intraperitoneal
transplantation of tumor [10]. Dalton’s lymphoma
tumor cells were preserved in the ascites form by
transplanting nearly 3×106 cells into the peritoneum
of inbred Swiss albino mice. After 8-10 days a
palpable tumor was observed and the tumor cells
were taken out with the help of a syringe and a gauge
needle. The S. interrupta leaf methanol extract was
treated to DLA injected cancer model mice, at a drug
of 100 mg/kg and 200 mg/kg body weight was orally
administered (Figure 2) to the tumor bearing animals.
Subsequently 15 days of treatment the extract
diminished the body weight growth, reduction in
packed cell volume, viable tumor cell count and the
life span of mice was increased, serum enzyme,
haematological parameters and lipid parameters were
all at normal range values when compared to the
cancer group mice, these findings suggested the leaf
methanol extract at 200 mg/kg dose was protective
against DLA [11]. However, one more research
group also studied DLA, where the whole methanol
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plant extract was examined haematological
parameters in male Swiss albino mice in which 200
mg/kg and 400 mg/kg dose suggestively increased
the Hgb content, RBC, platelets and decreased the
WBC count to normal levels and also showed the
percent increase of body weight [12]. All these
results suggest this plant was highly anticancer in
nature.
pathway. AO is a fluorescence dye that only stains
live cells and EtBr is also a fluorescence dye stains
orange dead cells, which interchelates with DNA. In
silico analysis showed that Kaempferol-3-O-b-Dglucopyranoside, a Secondary metabolite of
S.interrupta form 6 hydrogen bond interactions with
Arg 202, Gln 207, Gly 227, Gly 229, Thr 231 and
Ala 232 amino acids of human DEAD box RNA
helicase (DDX3 protein). The nuclear condensation
can be clearly seen from 100 μg/mL to 1000 μg/mL
concentration. The treated cell nuclei appeared to be
slightly smaller than normal nuclei, presuming these
cells have tails nuclei with apoptotic bodies [9].
Ongoing research from our group reveals some
important facts regarding the root extract of S.
interrupta. From this 34 molecules from ethyl acetate
extract were confirmed by GC-MS analysis. When all
of them docked in silico against VEGFR1 & R2
proteins have shown good network of hydrogen
bonding with Phe 1041, Asp 1040 for R1 and Cys
919, Glu 917, Phe 1047, Lys 912 and Thr 916 for R 2
amino acids respectively. This extract when treated
against blood vessels in the chick chorioallantoic
membrane (CAM) has significantly reduced the
intensity of forming blood vessels as a sign of
antiangiogenic nature. The toxicity studies of this
extract on brine shrimp’s confirmed us that it was
non-toxic and do not harm shrimps in any dosage
forms.
Anticancer activity in cell lines: Human cervical
cancer (HeLa) is an immortal cell line taken first
from Henrietta Lacks, a female patient died of cancer
on Oct 4th, 1951and human hepatic carcinoma
(HePG2) cell line which was a liver cell derived from
15-year-old Caucasian American male. The whole
methanol extract of the plant was applied in two
different cell lines (HeLa & HePG2) at different
concentrations. Half minimal inhibition reported
(IC50) for HeLa 211.5 μg/mL and HePG2 158.2
μg/mL. This data suggests that this plant extract
reduces the cervical and hepatic carcinoma cancers
[13]. Michigan cancer foundation (MCF-7) breast
cancer cell line was derived in 1970 from a 69-yearold Caucasian woman. MCF-7 cell lines taken from
the patient Frances Mallon died in 1970 and it was
unknown to the vast majority of cancer researchers.
Her cells were the foundation of modern knowledge
about breast cancer. Prostate cancer cells (PC-3) cell
lines were established in 1979 from bone metastasis
of grade IV of prostate cancer in a 62-year-old
Caucasian male. Earlier we have reported that the
root ethyl acetate extract of S. interrupta on both the
cell lines shown significant DNA damage and was
supported by the morphological changes such as
membrane blebbing, cell detachment and rounded
cell morphology when compared to the parental cells.
In addition, we observed few green cells (live), over
red cells (dead) based on the uptake of acridine
orange and ethidium bromide dyes. DNA
fragmentation assay was also reported in order to
investigate the cell death mechanism in which the
inter-nucleosomal breakdown of chromatin DNA,
resulting in ladder-like agarose electrophoresis of
degraded DNA. (Figure 3a & 3b) [14]. The apoptotic
nucleus was found in a dose dependent manner, the
shape of nucleolus completely vanished in at higher
concentrations. Another research group reported on a
leaf aqueous extract of S. interrupta against MCF-7
cancer cell lines to study antiproliferative and
anticancer effects using MTT and LDH assays. Cells
treated with S. interrupta extract, exhibited apoptotic
morphological changes in dose dependent manner,
such as cytoplasmic blebbing, enlarged, irregularshaped,
and
vacuolated
cytoplasm.
These
observations provide evidence that the compound
present in the extract also trigger the apoptotic
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Acute oral toxicity and ulcer studies: Acute oral
toxicity was an adverse effect of a substance for
single exposure or multiple. S. interrupta leaf
defatted methanol extract was reported for acute oral
toxicity in Swiss albino mice, the extract was not
shown toxic reactions, behavior changes as well as
mortality up to 2500 mg/kg and toxicity and
mortality was gained at 5000 mg/kg and thus safe
dose was considered to be 4000 mg/kg. Ulcer was a
discontinuity in the membrane which hinders the
normal function of the organ. Antiulcer studies were
performed in Aspirin and ethanol induced male
Wistar gastric ulcer rats using same extract, the
extract showed significant reduction in Aspirin
induced ulcer index (5.22+0.2) and ulcer formation
(60.42%). Similarly ethanol induced gastric ulcer was
reduced the ulcer index (5.2+0.1) and ulcer formation
(60.42%) [5].
Sophora interrupta activity on CNS: CNS is a part
of the nervous system consisting of the spinal cord
and brain. S. interrupta leaf methanol extract was
documented for Central Nervous System (CNS)
activity. A daily dose of 200mg/kg of extracts was
administered respectively to the swiss albino mice for
15 days, after which head dip test reported that
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exploratory behavior shown to be reduced, traction
tests and the rota rod test revealed the reduction in
the motor co-ordination of the tested animals when
compared with the control animals. The results
revealed that the methanol leaves extract of S.
interrupta, caused significant marked decline in
exploratory behavioral pattern in head dip test at
58.88 % protection, and a reduction in muscle
relaxant activity also observed by rota rod 55 %
protection and traction tests 55.02 % protection [15].
a) 3′,
4′-dimethoxy-7-(γ,
γ-dimethylallyloxy)
flavonol, which was an O-prenylated flavonol its
molecular mass 383.1451 and its molecular
formula C22H22O6. Although it was reported that it
was extracted from S. interrupta, its biological
activity was yet to be explored. Generally
flavonol sub class of flavonoids possess
phytoestrogenic or antioxidant properties [19].
For example a prenylated flavonoid was isolated
from S. flavescens shown significant inhibition of
acetyl cholinesterase activity [20].
b) 2′-hydroxy-3, 4-dimethoxychalcone its molecular
mass 284.306488 g/mol and molecular formula
C17H16O4. These chalcones are open chain
flavonoids
possess
a
wide
range
of
pharmacological activity such as antibacterial,
antitumor, anticancer, ant tubercular, antiinflammatory,
antioxidant,
antimalarial,
antileishmanial and also strong antioxidant
activity [21]. Chalcones also possess cytotoxic
activity on cancer cell lines [22].
c) Biochanin A was an O-methylated isoflavone. Its
molecular mass 284.26 g/mol and its molecular
formula C16H12O5. Biochanin-A found in cloves,
sprouts, peanuts, etc. It has putative benefits
towards cancer prophylaxis [23].
d) Kaempferol-3-O-β-D-glucopyranoside was first
isolated from Phytolacca americana plant source
and later it was also isolated from S. interrupta. It
was also known as Astragalin, with a molecular
mass 448.37 g/mol and the molecular formula
C21H20O11. The biological activity reported to be a
highly antiinflammatory effect and show good
antioxidant activity with DPPH stable free
radicals [24].
Anthelmintic activity of methanol leaf extract:
Helmintic parasites are cellular organisms, usually
can be seen with naked eyes in their mature stage.
They are worm-like organisms exists, and feed on
living host’s nutrient absorption, causing weakness
and diseases. In order to address this issue a research
team worked on leaf methanol extract against
Pheritima posthuma (model for Anthelmintic
studies). Results reported that within less time the
worms went paralyzed, i.e; at concentration 30
mg/mL extract has taken less time to cause paralysis
when compared with the standard [16].
Hepatoprotective activity: Chemicals that cause liver
injury are called hepatotoxins. There are many
chemicals and drugs which on over dosage lead to
hepatotoxic. The hepatoprotective activity was well
documented with the Leaf methanol extract against
carbon tetrachloride induced hepatotoxic male Wistar
rats [17]. The alterations in the serum markers such
as
alkaline
phosphatase
(ALP),
aspartate
transaminase (AST), alanine aminotransferase
(ALT), and total bilirubin resembles hepatotoxic
nature. Treatment with the methanol extract at a
concentration of 400 mg/mL exhibited protection in
altering the serum levels and also supported the work
with Histopathological studies of liver sections.
Hence S. interrupta proves one of the herbal
metabolite for treating liver dysfunctions.
Isolated active components and its biological roles:
A few of biologically active compounds, including
phenols, flavonol’s and flavones have been isolated
from roots of the plant. These compounds have been
reported to have different biological roles in disease
conditions, thus enabling potential application in
clinical research. A novel compound has been
isolated from the roots, (Figure 4) such as Oprenylated flavonol i.e; 3′, 4′-dimethoxy-7-(γ, γdimethylallyloxy)
flavonol.
2′-hydroxy-3,
4dimethoxychalcone was a well-known natural phenol.
Biochanin A was an isoflavone and well explored.
Kaempferol-3-O-β-D-glucopyranoside was also a
natural flavonol. These all compounds are
structurally elucidated by 1H and 13C-NMR [18].
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CONCLUSION
The current review reveals in a very interactive
manner, showing geographical region, parts used,
mechanism of action found to be having potent
anticancer, antiproliferative, antioxidant, anthelmintic
and CNS activities. This plant has been reported to
contain phytoconstituents such as prenylated
flavonoids, chalcones, biochanin-A and Kaempferol.
The compounds which were isolated from this plant
have
pharmacological
and
toxicological
investigations both in vitro and in vivo. And these can
be lead molecules in human clinical trials. Thereby,
the review can help researchers to know the work
done so far on S. interrupta. It further helps in
modern drug development and serves the purpose of
Ayurvedic formulation development in treating
diseases by proving clinical safety, reliability and
efficacy.
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ACKNOWLEDGEMENTS
Authors are very thankful to K L E F University
management for their continuous support.
CONFLICT OF INTEREST
The authors have no conflicts of interest to declare.
Table 1: Taxonomic status of Sophora interrupta
Domain
Eukaryota
Kingdom
Plantae
Sub-kingdom
Viridaeplantae
Phylum
Tracheophyta
Class
Spermatopsida
Sub-class
Magnoliidae
Super Order
Rosanae
Order
Fabales
Family
Fabaceae
Subfamily
Faboideae
Tribe
Sophoreae
Genus
Sophora
Species
interrupta
Table 2: Different Sophora species with geographical locations in worldwide
S. No
Sophora species
Geographical location
Latitude & Longitude
1
S. interrupta
Tirumala hills
13.6 & 79.3
2
S. microphylla
a) Chatham Island, Chile b) Gough Island.
3
4
5
S. alopecuroides
S. viciifolia
S. tomentosa
6
S. tetraptera
7
8
S. subprostrata
S. secundiflora
9
10
11
12
13
14
15
16
S. prostrata
S. leachiana
S. koreensis
S. exigua
S. fraseri
S. stenophylla
S. nuttalliana
S. mollis
Karachi
Yun-Nan; China
a) Tokyo; Japan.
b) Texas; U.S.A
Landcare Research;
New Zealand
Shimizu-shi Shizuoka; Japan
a) Amistad Recreation Area near Del Rio,
Texas.
b) Peshawar; Pakistan.
New Zealand
USA
Incheon, South Korea
Thailand
Benth; Australia
Hildale, Washington County, UT
West of Cedar City, Iron County, UT
Peshawar; Pakistan
a) -50.4 & -72.7
b) -40.3 & -9.9
25.01 & 67.06
25.1 & 101.8
a) 35.6 & 139.7
b) 31.1 & -100.0
-43.6 & 172.4
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35.08 & 138.5
a) 29.4 & -101.05
b) 33.9 & 71.5
-43.3 & 172.4
-37.6 & -95.66
37.4 & 126.6
13.03 & 101.4
-41.5 & 147.7
37.01 & -112.9
37.6 & -113.1
33.9 & 71.5
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17
S. macrocarpa
18
S. japonica
19
S. flavescens
20
21
22
23
S. davidii
S. chrysophylla
S. alopecuroides
S. tonkinensis
24
25
26
27
28
29
30
31
32
33
34
35
36
S. tetraptera
S. yunnanensis
S. velutina
S. arizonica
S. secundiflora
S. gypsophila
S. exigua
S. toromiro
S. longicarinata
S. fernandeziana
S. masafuerana
S. macnabiana
S. howinsula
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La Dormida Paes, North of Santiago,
Chile
a)
Nanjing, (People’s Republic)
China.
b)
University of California.
a) Lanzhou, China
b) Shanxi Province, China.
c) Botanical Garden of Wonkwang
University, Iksan, Korea.
d) Seoul, Republic of Korea.
e) Japan
f) Transbaikalia and Primorsky regions
and Agin Buryat
Autonomous Okrug, Russia.
g) Gansu Province, China.
h) Taejon, Korea.
i) Kangwon Province, Korea.
Texas
Pohakuloa; Hawaiian islands
Xinjiang, China
a) South China.
b) Guangxi Province
Auckland, New Zealand
China
Zimbabwe National Herbarium
Mohave, Arizona, U.S.A.
Kingsville, Kleberg. Texas.
Edo. Chihuahua, Mexico
Northeastern Thailand
Easter island
New Zealand
Juan Fernandez islands
Juan Fernandez islands
Gough island
Lord howe island; Caribbean
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-33.6 & -70.3
a) 32.0 & 118.7
b) 37.2 & -119.2
a) 36.0 & 103.7
b) 37.6 & 112.3
c) 35.9 & 126.9
d) 37.5 & 126.9
e) 37.4 & 136.4
f) 53.7 & 114.9
g) 37.6 & 100.5
h) 36.3 & 127.3
i) 37.8 & 128.2
31.1 & -100.07
23.5 & -166.7
41.7 & 84.9
a)
25.5 & 112.8
b)
23.6 & 108.2
-36.8 & 174.8
35.8 & 104.1
-19.01 & 29.15
35.6 & -113.6
27.5 & -97.8
28.6 & -106.1
16.4 & 102.7
-27.1 & -109.3
-43.3 & 172.4
-33.6 & -78.8
-33.6 & -78.8
-40.3 & -9.9
-31.5 & 159.07
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Figure 1: Pictographic representation of Sophora species in world map with serial numbers referring table 2
Figure 2: Sophora interrupta treating Dalton’s Ascites Lymphoma (DLA)
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Figure 3: a) MCF-7 & PC-3 cells representing Apoptosis assay by Acridine orange/ Ethidium bromide. Early
and late apoptosis depicted by orange and red colored cells. b) Insilico docking against DDX3 (PDB ID: 2I4I)
with AMP; Kaempferol.
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Figure 4. Compounds isolated from S. interrupta root are a) 3′, 4′-dimethoxy-7-(γ, γ- dimethylallyloxy) flavonol
b) 2′-hydroxy-3, 4-dimethoxychalcone c) Biochanin A d) Kaempferol-3-O-β-D-glucopyranoside
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